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Brain Synaptosome

The Experts below are selected from a list of 60 Experts worldwide ranked by ideXlab platform

Frode Fonnum – 1st expert on this subject based on the ideXlab platform

  • Discussion of the Role of the Extracellular Signal-Regulated Kinase-Phospholipase A_2 Pathway in Production of Reactive Oxygen Species in Alzheimer’s Disease
    Neurochemical Research, 2003
    Co-Authors: Jannike M. Andersen, Oddvar Myhre, Frode Fonnum

    Abstract:

    In this paper we show that exposure of a rat Brain Synaptosome fraction to the amyloid beta peptide fragment βA(25-35), but not the inverted peptide βA(35-25), stimulated production of reactive oxygen species (ROS) in a concentration- and time-dependent manner. The ROS formation was attenuated by the tyrosine kinase inhibitor genistein, the mitogen-activated protein kinase inhibitor U0126, and the phospholipase A_2 (PLA_2) inhibitor 7,7-dimethyl-(5Z,8Z)-eicosadienoic acid. This strongly suggests that βA(25-35) stimulated ROS production through an extracellular signal-regulated kinase-PLA_2-dependent pathway. The interaction between these enzymes and their possible involvement in free radical formation in Alzheimer’s disease are discussed.

  • the effect of aliphatic naphthenic and aromatic hydrocarbons on production of reactive oxygen species and reactive nitrogen species in rat Brain Synaptosome fraction the involvement of calcium nitric oxide synthase mitochondria and phospholipase a
    Biochemical Pharmacology, 2001
    Co-Authors: Oddvar Myhre, Frode Fonnum

    Abstract:

    Abstract This study investigated the effects of C7 and C9 aliphatic (n-heptane, n-nonane), naphthenic (methylcyclohexane, 1,2,4-trimethylcyclohexane (TMCH)) and aromatic (toluene, 1,2,4-trimethylbenzene (TMB)) hydrocarbons on the production of reactive oxygen species (ROS) and reactive nitrogen species (RNS) in rat Brain Synaptosome fraction. Methyl mercury (MeHg) was included as a positive control. Exposure of the Synaptosomes to the hydrocarbons produced a concentration-dependent linear increase in the formation of the fluorescence of 2′,7′-dichlorofluorescein (DCF) as a measure of the production of ROS and RNS. Formation of RNS was demonstrated by preincubation of the Synaptosome fraction with the neuronal nitric oxide synthase (nNOS) inhibitor Nω-nitro- l -arginine methyl ester (L-NAME), which reduced the MeHg and TMCH-stimulated fluorescence by 51% and 65%, respectively. The naphthenic hydrocarbon TMCH showed the strongest potential for ROS and RNS formation in rat Brain Synaptosomes, followed by TMB, toluene, n-nonane, n-heptane, and methylcyclohexane, respectively. TMCH was selected for mechanistic studies of the formation of ROS. Both MeHg and TMCH induced an increase in intracellular calcium concentration [Ca2+]i as measured with Fura-2. Blockade of voltage-dependent Ca2+ channels with lanthanum prior to stimulation with MeHg and TMCH led to a reduction in the ROS/RNS formation of 72% and 70%, respectively. Furthermore, addition of cyclosporin A (CSA), a blocker of the mitochondrial permeability transition pore (MTP), lowered both the MeHg and TMCH-elevated DCF fluorescence by 72% and 59%. Preincubation of the Synaptosome fraction with the protein tyrosine kinase inhibitor genistein lowered the MeHg and TMCH-stimulated fluorescence by 85% and 91%, respectively. Addition of the extracellular signal-regulated protein kinase (MEK)-1 and -2 inhibitor U0126 reduced the fluorescence stimulated by MeHg and TMCH by 62% and 63%. Furthermore, the protein kinase C inhibitor bisindolylmaleimide reduced the fluorescence stimulated by MeHg and TMCH by 52% and 56%. The compound 1-(6-[17beta-3-methoxyestra- 1,3,5(10)-trien- 17-yl]-aminohexyl)-1H-pyrrole-2,5-dione (U73122), which inhibits phospholipase C, was shown to decrease the ROS and RNS formation induced by MeHg and TMCH by 49% and 64%, respectively. The phospholipase A2 (PLA2) inhibitor 7,7-dimethyl eicosadienoic acid (DEDA) reduced fluorescence in response to MeHg and TMCH by 49% and 54%. Simultaneous addition of L-NAME, CSA, and DEDA to the Synaptosome fraction totally abolished the DCF fluorescence. In conclusion, C7 and C9 aliphatic, naphthenic, and aromatic hydrocarbons stimulated formation of ROS and RNS in rat Brain Synaptosomes. The naphthenic hydrocarbon TMCH stimulated formation of ROS and RNS in the Synaptosomes through Ca2+-dependent activation of PLA2 and nNOS, and through increased transition permeability of the MTP. Exposure of humans to the naphthenic hydrocarbon TMCH may stimulate formation of free radicals in the Brain, which may be a key factor leading to neurotoxicity.

Oddvar Myhre – 2nd expert on this subject based on the ideXlab platform

  • Discussion of the Role of the Extracellular Signal-Regulated Kinase-Phospholipase A_2 Pathway in Production of Reactive Oxygen Species in Alzheimer’s Disease
    Neurochemical Research, 2003
    Co-Authors: Jannike M. Andersen, Oddvar Myhre, Frode Fonnum

    Abstract:

    In this paper we show that exposure of a rat Brain Synaptosome fraction to the amyloid beta peptide fragment βA(25-35), but not the inverted peptide βA(35-25), stimulated production of reactive oxygen species (ROS) in a concentration- and time-dependent manner. The ROS formation was attenuated by the tyrosine kinase inhibitor genistein, the mitogen-activated protein kinase inhibitor U0126, and the phospholipase A_2 (PLA_2) inhibitor 7,7-dimethyl-(5Z,8Z)-eicosadienoic acid. This strongly suggests that βA(25-35) stimulated ROS production through an extracellular signal-regulated kinase-PLA_2-dependent pathway. The interaction between these enzymes and their possible involvement in free radical formation in Alzheimer’s disease are discussed.

  • the effect of aliphatic naphthenic and aromatic hydrocarbons on production of reactive oxygen species and reactive nitrogen species in rat Brain Synaptosome fraction the involvement of calcium nitric oxide synthase mitochondria and phospholipase a
    Biochemical Pharmacology, 2001
    Co-Authors: Oddvar Myhre, Frode Fonnum

    Abstract:

    Abstract This study investigated the effects of C7 and C9 aliphatic (n-heptane, n-nonane), naphthenic (methylcyclohexane, 1,2,4-trimethylcyclohexane (TMCH)) and aromatic (toluene, 1,2,4-trimethylbenzene (TMB)) hydrocarbons on the production of reactive oxygen species (ROS) and reactive nitrogen species (RNS) in rat Brain Synaptosome fraction. Methyl mercury (MeHg) was included as a positive control. Exposure of the Synaptosomes to the hydrocarbons produced a concentration-dependent linear increase in the formation of the fluorescence of 2′,7′-dichlorofluorescein (DCF) as a measure of the production of ROS and RNS. Formation of RNS was demonstrated by preincubation of the Synaptosome fraction with the neuronal nitric oxide synthase (nNOS) inhibitor Nω-nitro- l -arginine methyl ester (L-NAME), which reduced the MeHg and TMCH-stimulated fluorescence by 51% and 65%, respectively. The naphthenic hydrocarbon TMCH showed the strongest potential for ROS and RNS formation in rat Brain Synaptosomes, followed by TMB, toluene, n-nonane, n-heptane, and methylcyclohexane, respectively. TMCH was selected for mechanistic studies of the formation of ROS. Both MeHg and TMCH induced an increase in intracellular calcium concentration [Ca2+]i as measured with Fura-2. Blockade of voltage-dependent Ca2+ channels with lanthanum prior to stimulation with MeHg and TMCH led to a reduction in the ROS/RNS formation of 72% and 70%, respectively. Furthermore, addition of cyclosporin A (CSA), a blocker of the mitochondrial permeability transition pore (MTP), lowered both the MeHg and TMCH-elevated DCF fluorescence by 72% and 59%. Preincubation of the Synaptosome fraction with the protein tyrosine kinase inhibitor genistein lowered the MeHg and TMCH-stimulated fluorescence by 85% and 91%, respectively. Addition of the extracellular signal-regulated protein kinase (MEK)-1 and -2 inhibitor U0126 reduced the fluorescence stimulated by MeHg and TMCH by 62% and 63%. Furthermore, the protein kinase C inhibitor bisindolylmaleimide reduced the fluorescence stimulated by MeHg and TMCH by 52% and 56%. The compound 1-(6-[17beta-3-methoxyestra- 1,3,5(10)-trien- 17-yl]-aminohexyl)-1H-pyrrole-2,5-dione (U73122), which inhibits phospholipase C, was shown to decrease the ROS and RNS formation induced by MeHg and TMCH by 49% and 64%, respectively. The phospholipase A2 (PLA2) inhibitor 7,7-dimethyl eicosadienoic acid (DEDA) reduced fluorescence in response to MeHg and TMCH by 49% and 54%. Simultaneous addition of L-NAME, CSA, and DEDA to the Synaptosome fraction totally abolished the DCF fluorescence. In conclusion, C7 and C9 aliphatic, naphthenic, and aromatic hydrocarbons stimulated formation of ROS and RNS in rat Brain Synaptosomes. The naphthenic hydrocarbon TMCH stimulated formation of ROS and RNS in the Synaptosomes through Ca2+-dependent activation of PLA2 and nNOS, and through increased transition permeability of the MTP. Exposure of humans to the naphthenic hydrocarbon TMCH may stimulate formation of free radicals in the Brain, which may be a key factor leading to neurotoxicity.

Susumu Otomo – 3rd expert on this subject based on the ideXlab platform

  • blockade of voltage dependent 42k efflux from rat Brain Synaptosome by minaprine and tetrahydroaminoacridine
    Life Sciences, 1991
    Co-Authors: Shigeyuki Chaki, Makoto Muramatsu, Susumu Otomo

    Abstract:

    Abstract The effect of minaprine (3-(2-morpholinoethylamino)- 4-methyl-6-phenylpyridazine) on the K + channels was studied by means of 42 K efflux from rat Brain Synaptosomes, comparing the effects of 4-aminopyridine and 9-amino-1,2,3,4-tetrahydroacridine (THA). 42 K efflux from rat Brain Synaptosomes was classified into five components: a resting component (R), a rapidly inactivating, voltage-dependent component (T), a slowly inactivating, voltage-dependent component (S) and a voltage-dependent, Ca 2+ -dependent component which is divided into a fast phase (C T ) and a slower phase (C S ). 4-Aminopyridine selectively inhibited 42 K efflux of component T. THA blocked both S and T components. The inhibitory effect of THA on the 42 K efflux of component S was quite pronounced compared with that of component T. Minaprine inhibited the 42 K efflux of components S and T but the inhibitory effect on component S was observed with a lower dose of minaprine than that needed for the effect on component T. Minaprine had no effect on the Ca 2+ -dependent component while THA blocked component C T . 42 K efflux of the resting component was not changed by minaprine, THA or 4- aminopyridine. These results suggest that minaprine blocks Ca 2+ independent voltage-dependent K + channel is involved in the pharmacological actions of minaprine.